mohler

Peter J. Mohler, Ph.D.

Associate Professor

Office: 2267 CBRB

Lab: 2283 CBRB

Phone: (319) 335-9691

Lab: (319) 335-9679

FAX: (319) 353-5552

Email: peter-mohler@uiowa.edu

Education and Other Appointments

  • 2000 - Ph.D., University of North Carolina, Chapel Hill, NC
  • 2000-2004 - Postdoc, Howard Hughes Medical Institute, Duke University, Durham, NC
  • Associate Professor: Medicine

Research Interests

Our research focuses on the molecular mechanisms underlying ion channel and transporter targeting in cardiac and other excitable cells. In particular, we are interested in the role of membrane-associated ankyrin family of polypeptides in the targeting and function of ion channels and transporters. Our work establishes that loss-of-function mutation in ankyrin-B is the basis for a new human cardiac arrhythmia syndrome associated with sinus node dysfunction, repolarization defects, and polymorphic tachyarrhythmia in response to stress and/or exercise (“ankyrin-B syndrome”).

Additionally, our work revealed that reduction of ankyrin-B in mice results in reduced levels and abnormal localization of Na/Ca exchanger, Na/K ATPase, and InsP3 receptor at T-tubule/SR sites in cardiomyocytes and leads to altered Ca2+ signaling and extrasystoles that provide a rationale for the arrhythmia. A second line of work in the lab is focused on the role of ankyrin-G for targeting voltage-gated Na channels in heart. These studies establish a physiological requirement for ankyrins in localization of a variety of ion channels in excitable membranes in the heart and demonstrate a new class of functional ‘channelopathies’ due to abnormal cellular localization of functionally-related ion channels and transporters.

Selected Publications

1. Anderson ME, Mohler PJ. MicroRNA may have macro effect on sudden death. Nat Med. 2007;13(4):410-411.

2. Bhasin N, Cunha SR, Mudannayake M, Gigena MS, Rogers TB, Mohler PJ. Molecular basis for PP2A regulatory subunit B56{alpha} targeting in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2007;293(1):H109-119.

3. Cunha SR, Bhasin N, Mohler PJ. Targeting and stability of na/ca exchanger 1 in cardiomyocytes requires direct interaction with the membrane adaptor ankyrin-B. J Biol Chem. 2007;282(7):4875-4883.

4. Mohler PJ, Le Scouarnec S, Denjoy I, Lowe JS, Guicheney P, Caron L, Driskell IM, Schott JJ, Norris K, Leenhardt A, Kim RB, Escande D, Roden DM. Defining the cellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes. Circulation. 2007;115(4):432-441.

5. Cunha SR, Le Scouarnec S, Schott JJ, Mohler PJ. Exon organization and novel alternative splicing of the human ANK2 gene: Implications for cardiac function and human cardiac disease. J Mol Cell Cardiol. 2008.

6. Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, O'Donnell SE, Aykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, Anderson ME. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell. 2008;133(3):462-474.

7. Hund TJ, Ziman AP, Lederer WJ, Mohler PJ. The cardiac IP(3) receptor: Uncovering the role of "the other" calcium-release channel. J Mol Cell Cardiol. 2008.

8. Kline CF, Cunha SR, Lowe JS, Hund TJ, Mohler PJ. Revisiting ankyrin-InsP3 receptor interactions: ankyrin-B associates with the cytoplasmic N-terminus of the InsP3 receptor. J Cell Biochem. 2008;104(4):1244-1253.

9. Le Scouarnec S, Bhasin N, Vieyres C, Hund TJ, Cunha SR, Koval O, Marionneau C, Chen B, Wu Y, Demolombe S, Song LS, Le Marec H, Probst V, Schott JJ, Anderson ME, Mohler PJ. Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease. Proc Natl Acad Sci U S A. 2008.

10. Lowe JS, Palygin O, Bhasin N, Hund TJ, Boyden PA, Shibata E, Anderson ME, Mohler PJ. Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. J Cell Biol. 2008;180(1):173-186.

11. Cunha SR, Mohler PJ. Obscurin targets ankyrin-B and protein phosphatase 2A to the cardiac M-line. J Biol Chem. 2008.